2015 ISAKOS Biennial Congress ePoster #2402
Are the Symptoms of Calcific Tendonitis Due to Neoinnervation and/or Neovascularisation?
Lisa Hackett, AMS, Sydney, NSW AUSTRALIA
Neal Millar, MD, PhD, FRCS, Glascow, Scotland UNITED KINGDOM
Patrick H. Lam, PhD, Sydney, NSW AUSTRALIA
George A. Murrell, MD, PhD, Sydney, NSW AUSTRALIA
St. George Hospital Campus, UNSW, Sydney, NSW, AUSTRALIA
FDA Status Not Applicable
Summary: This study shows a very significant concomitant eight (8) fold increase in mast cells, macrophages, and neo-neurovascular infiltration in the tendons of patients with calcific tendonitis.
Calcific tendonitis is a significant cause of pain and dysfunction in the shoulder. There is a lack of consensus on the pathophysiology of calcific tendonitis while recent studies have shown a link between nerve ingrowth, neovascularization and pain in tendinopathy.
The aim of this study was to determine whether there is evidence of neoinnervation and/or neovascularisation in calcific tendinitis lesions of the shoulder.
This was a prospective case control study. After regional anaesthesia, ultrasound was used to identify calcium within the tendon and a breast biopsy localisation needle was placed in the calcific region in patients with calcific supraspinatus tendonitis. At arthroscopy the needle was utilized to identify and subsequently remove the calcium from the supraspinatus tendon. Small 2mm samples were taken from the supraspinatus tendon adjacent to the calcific lesion (calcific tendonitis, n = 7), torn supraspinatus tendon of patients undergoing rotator cuff repair (RCT, n = 6 ) and the subscapularis of patients undergoing stabilisation surgery (control, n = 6 ). Samples were paraffin embedded, sectioned and stained with hematoxylin and eosin. The following antibodies were used for immunohistochemical evaluation; macrophages (CD68), M2 macrophages (CD202), mast cells (mast cell tryptase), T cells (CD3), vascular endothelium (CD34) and general nerve marker (PGP9.5) utilising the appropriate isotype controls
There were no significant differences in T-cell count between the calcific tendonitis group and the RCT group; however both the calcific tendonitis and RCT group had 5-6 fold higher T-cell counts compared to the control group (p < 0.001; p < 0.004).
There was a 3-8 fold increase of nerve markers, neovascularisation, macrophages, M2 macrophages, and mast cells in the calcific tendonitis group compared to the RCT group (p < 0.0002) and control group (p < 0.0001). There were approximately three times more of each markers in tendon from patients with calcific tendonitis compared to tendon from patients with rotator cuff tears.
Increased blood vessels positively correlated with more frequent pain during sleep (spearman correlation, r = 0.6, p < 0.01) and extreme pain (r = 0.6, p < 0.01). Increase blood vessels also positively correlated with increased CD68 macrophages (r = 0.5, p < 0.02), M2 macrophages (r = 0. 6, p < 0.01), mast cells (r = 0.6, p < 0.005) and T-cells (r = 0.7, p<0.001). Increase nerve counts positively correlated with more frequent extreme pain (r = 0.6, p < 0.01), with increase neovascularisation (r = 0.7, p < 0.01), counts of CD68 macrophages (r = 0.6, p < 0.04), M2 macrophages (r = 0.6, p < 0.01), mast cells (r = 0.8, p < 0.0001), and T-cells (r = 0.6, p < 0.01).
To our knowledge this is the first time markers for nerves and blood vessels have been evaluated in tendon from patients with calcific tendonitis. This study shows a very significant concomitant eight (8) fold increase in mast cells, macrophages, and neo-neurovascular infiltration in the tendons of patients with calcific tendonitis. These increases in neo-neurovascular infiltration were strongly associated with shoulder pain. The data is consistent with the hypothesis that deposition of calcific material is associated with a foreign body immune reaction, new blood vessels and nerves, and the very severe pain often noted in patients with calcific tendonitis.